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From Proteopedia
Crystal Structure of Human serum albumin complexed with Lidocaine
Structural highlights
Disease[ALBU_HUMAN] Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM:103600]. FDH is a form of euthyroid hyperthyroxinemia that is due to increased affinity of ALB for T(4). It is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasian population.[1] [2] [3] [4] Function[ALBU_HUMAN] Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.[5] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman serum albumin (HSA), the major protein component in blood plasma and in extravascular spaces, is known to participate in the binding and transport of a variety of endogenous and exogenous organic compounds with anionic or electronegative features. We here report on the 3.3A resolution crystal structure of HSA complexed with the cationic, and widely used, anesthetic lidocaine. We find that lidocaine and HSA co-crystallise as a dimer in the unusual space group I4(1). The dimer consists of one HSA molecule without ligand and one HSA molecule with a single, bound lidocaine. HSA is a heart-shaped protein composed of three homologous helical domains (I-III), which can be subdivided into two subdomains (A and B), and lidocaine binds to a unique site formed by residues from subdomain IB facing the central, interdomain crevice. In the crystal, binding seems to introduce only local conformational changes in the protein. According to intrinsic fluorescence experiments with aqueous HSA binding results in widespread conformational changes involving Trp214 in subdomain IIA. Results obtained with equilibrium dialysis and isothermal titration calorimetry show that lidocaine binding is of a low affinity and occurs at one discrete binding site in accordance with the X-ray data. Another crystal form of ligand-free HSA obtained in the presence of ammonium sulphate was determined at 2.3A resolution revealing a sulphate ion accepting cavity at the surface of subdomain IIIA. The present results contribute to a further characterisation of the exceptional binding properties of HSA. Crystallographic analysis reveals a unique lidocaine binding site on human serum albumin.,Hein KL, Kragh-Hansen U, Morth JP, Jeppesen MD, Otzen D, Moller JV, Nissen P J Struct Biol. 2010 Sep;171(3):353-60. Epub 2010 Mar 27. PMID:20347991[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Hein, K L | Kragh-Hansen, U | Morth, J P | Nissen, P | Albumin | Alternative splicing | Carrier protein | Cleavage on pair of basic residue | Copper | Disease mutation | Disulfide bond | Drug-binding | Glycation | Glycoprotein | Lidocaine | Lipid-binding | Metal-binding | Phosphoprotein | Polymorphism | Secreted | Transport protein
